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Potassium Phosphate, Tribasic → 2-(4-(difluoromethoxy)-N-(1-(4-(pyrimidin-5-yl)phenyl)cyclobutyl)phenylsulfonamido) acetic acid

HRID 1951749
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HRID 1951749 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([N:12]([CH2:26][C:27]([OH:29])=[O:28])[S:13]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH:23]([F:25])[F:24])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C(O)CCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:24][CH:23]([F:25])[O:22][C:19]1[CH:20]=[CH:21][C:16]([S:13]([N:12]([CH2:26][C:27]([OH:29])=[O:28])[C:8]2([C:5]3[CH:6]=[CH:7][C:2]([C:34]4[CH:35]=[N:30][CH:31]=[N:32][CH:33]=4)=[CH:3][CH:4]=3)[CH2:11][CH2:10][CH2:9]2)(=[O:15])=[O:14])=[CH:17][CH:18]=1
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7

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HCID 62657Potassium Phosphate, TribasicHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 53373333HCID 53373333, 화합물

생성물 1

HCID 533734692-(4-(difluoromethoxy)-N-(1-(4-(pyrimidin-5-yl)phenyl)cyclobutyl)phenylsulfonamido) acetic acid수율 16%

시약·촉매·용매

2
HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 2631-Butanol용매

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온도
100 °C

실험 절차

To a solution of 2-(N-(1-(4-bromophenyl)cyclobutyl)-4-(difluoromethoxy)phenylsulfonamido) acetic acid (20 mg, 0.041 mmol) in n-butanol (2 mL) was added pyrimidin-5-ylboronic acid (7.58 mg, 0.061 mmol), followed by potassium phosphate (17.32 mg, 0.082 mmol) and Pd2 dba3 (2.345 mg, 4.08 μmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (3.89 mg, 8.16 μmol). The mixture was degassed and flushed with argon and then shook at 100° C. for 3 h. The resultant mixture was filtered and the filtrate purified using Shimadzu prep HPLC employing an ACN/water and 0.1% TFA buffer with a Xterra column, 30 mm×100 mm, Gradient over 15 min; Starting conc: 10% B; Ending conc: 100% B. The solvent was removed in vacuo to give 3.3 mg (16% yield, 95% pure) of the title compound as a light gray solid. ESI-MS m/z 490 (MH+), 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.67 (q, J=10.07 Hz, 1H), 1.78-1.92 (m, 1H), 2.63 (t, J=8.70 Hz, 2H), 2.86 (d, J=2.44 Hz, 2H), 4.21 (s, 3H), 6.58 (t, J=75.00 Hz, 1H), 7.09 (d, J=8.55 Hz, 2H), 7.54 (d, J=8.24 Hz, 2H), 7.67 (dd, J=14.80, 8.70 Hz, 4H), 9.10 (s, 2H), 9.31 (s, 1 H).

후처리

  1. customThe mixture was degassed
  2. customflushed with argon
  3. filtrationThe resultant mixture was filtered
  4. customthe filtrate purified
  5. customover 15 min
  6. customThe solvent was removed in vacuo

출처 및 근거

ORD 기록
ord-eaac1630d56f458e98af268a5c39d972
출처 데이터셋
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08404741B2

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